Bcl-w promotes cell invasion by blocking the invasion-suppressing action of Bax

Cellular Signalling
Eun Mi KimHong-Duck Um

Abstract

The Bcl-2 family members are key regulators of cellular viability, either promoting or suppressing cell death. Recent reports have indicated that the pro-survival members (Bcl-w, Bcl-XL, and others) also enhance the migratory and invasive potentials of cancer cells, although the mechanisms underlying this phenomenon have yet to be adequately elucidated. Herein, by using human cancer cells and mouse embryonic fibroblasts, we demonstrate that Bcl-w functions in the mitochondria to increase the levels of reactive oxygen species (ROS), which subsequently stimulates the invasion-promoting signaling pathway. By way of contrast, Bax,a member of the multidomain pro-apoptotic group (Bax and Bak), was found to reduce ROS levels, thereby suppressing cell invasion. Analyses of the functional relationship between Bcl-w and Bax have shown that Bcl-w requires Bax for promoting cell invasion, whereas Bax suppresses cell invasion in a Bcl-win dependent manner. By using a Bcl-w mutant (Bcl-w/G94A) that was found not to bind to Bax, we have further determined that Bcl-w should bind to Bax to promote cell invasion. Overall, the results indicate that Bcl-w enhances cellular invasiveness by binding to Bax and subsequently blocking its invasion suppr...Continue Reading

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Citations

Mar 22, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Katharina E CoskerRosalind A Segal
Aug 20, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Eun Mi KimHong-Duck Um
Feb 27, 2013·Cancer Letters·Chan-Hun JungHong-Duck Um
Sep 5, 2019·Cells·Yujing ChiJichun Yang
Feb 20, 2016·Oncotarget·Chan-Hun JungHong-Duck Um
Apr 23, 2020·Cell Death & Disease·Mariusz L Hartman, Malgorzata Czyz
May 10, 2018·Frontiers in Oncology·Andrea MattareiLucia Biasutto
Apr 29, 2018·Cancer Research·Eun Mi KimHong-Duck Um
Jan 28, 2021·Biochemical and Biophysical Research Communications·Jihyun LeeHong-Duck Um
Jun 3, 2021·International Journal of Molecular Sciences·Dennis M TimmermanLeendert H J Looijenga
Nov 19, 2021·Journal of Cellular Biochemistry·Merve KulbayJacques Bernier

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BCL-2 Family Proteins

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